Mechanism of Hemostasis
Understanding the mechanism of hemostasis is crucial to the surgical treatment of the dental implant patient. Hemostasis is defined as a highly regulated process that maintains blood flow through the vasculature simultaneously as a thrombotic response to the tissue damage.2 Biologically, hemostasis requires a complex cascade of interactions involving the vessel wall, platelets, and fibrin coagulation and fibrinolytic systems. For this to occur, there are three reactions—primary, secondary, and tertiary—that act simultaneously (Fig. 7.2).
Vascular and Platelet Activity (Primary Hemostasis).
The first phase of hemostasis occurs immediately after blood vessel damage as a result of vasoconstriction. This reduces blood flow, limits the amount of blood loss, enhances platelet adherence, and activates coagulation.3 Vasoconstriction is triggered by direct injury to vascular smooth muscle, chemicals released by endothelial cells and platelets, and reflexes initiated by pain receptors. This spasm response becomes greater as injury increases and is more effective on smaller blood vessels.4 Mechanical blockage occurs by platelets adhering to exposed collagen (platelet adhesion), which release cytokines (serotonin, thromboxane A2, and endothelin1) into the area of tissue injury.3 This plug formation is activated by von Willebrand factor (vWF), a glycoprotein found in plasma. The platelets forming the plug will release chemical messengers such as adenosine diphosphate (ADP), fibronectin, thrombospondin, fibrinogen and PDGF, which causes more platelets to aggregate and enhance vascular spasms.5 As more platelets adhere and release their chemicals, a positive feedback loop results, which ends in the formation of a platelet plug. Drugs that affect primary hemostasis include aspirin and clopidogrel, which affect platelet function and prevent thrombosis.
Blood Coagulation (Secondary Hemostasis).
The second step in the process of hemostasis occurs when the clotting factors within the blood plasma form a collagen fiber called fibrin. This fibrin forms a mesh, collecting red and white blood cells that strengthen the clot, which is termed the coagulation cascade.6 The coagulation cascade is divided into three pathways, the intrinsic pathway, extrinsic pathway, and coagulation cascade.
The intrinsic pathway (contact activation pathway) requires clotting factors VII, IX, X, XI, and XII as well as proteins and calcium ions and phospholipids secreted by platelets. This pathway has a less significant effect on hemostasis in comparisons to the extrinsic pathway under normal physiologic conditions.
The extrinsic pathway (tissue factor pathway) is the main pathway that generates a “thrombin burst,” which involves a feedback activation role where thrombin is released rapidly. Thrombin activates factors V and VII, which in turn activate other factors to continue the coagulation process.
Common pathway involves factor X generation of thrombin from prothrombin. Thrombin then activates factors XI and VIII, which amplify the coagulation cascade, releasing more thrombin. Thrombin then causes fibrinogen to form, which results in cross-linked fibrin. Drugs that effect secondary hemostasis include warfarin, the direct thrombin inhibitors, and heparin5,7 (Fig. 7.3).
Fibrinolysis (Tertiary Hemostasis).
The last phase of hemostasis involves the formation of plasmin from plasminogen. Plasmin lyses fibrinogen and fibrin. This releases fibrin degradation products, which are cleared by the kidney and liver. Thus the fibrin clot, the final product of coagulation, is broken down (fibrinolysis). A drug that inhibits the tertiary hemostasis is tranexamic acid.8
Factors Contributing to Intraoperative Bleeding
Many factors may contribute to intraoperative bleeding. The incidence of bleeding episodes during dental surgery has been shown to be up to 4% of patients exhibiting normal hemostasis. In chronically anticoagulated patients, studies have shown bleeding episodes to be in the range of 8.6% to 32.1%.9 Although rare, bleeding during dental implant surgery may be life threatening. The implant clinician must be conscious of the signs and symptoms of a potential bleeding emergency. If the patient displays any signs of shock (tachycardia, hypotension, cold/clammy skin, lethargy), immediate medical assistance is recommended along with immediate intravenous fluid replacement to replenish the intravascular volume and reestablish tissue perfusion.
The first step in preventing bleeding issues is with the medical history (see Chapter 2). A thorough review of the medical history may alert the clinician to many factors that may ultimately potentiate intraoperative bleeding. A detailed medical history screening should evaluate current and past systemic disorders, medication list, and history of past bleeding episodes.
The most common class of medications that predispose patients to bleeding problems is the anticoagulants. These may include Coumadin derivatives, antiplatelets, direct thrombin inhibitors, and herbal supplements. In most cases of Coumadin-based medications, discontinuation is not recommended for routine dental implant procedures because local hemostatic measures are effective in managing hemorrhage. Stopping these medications may have deleterious effects and have a greater chance of creating complications for the patient. The patient’s physician should always be consulted and the implant clinician should NEVER unilaterally cease or modify any medication that was prescribed by a physician (Table 7.1).
|Coumadin (warfarin)||Pradaxa (dabigatran)||Xarelto (rivaroxaban)||Eliquis (apixapan)|
|Mode of action||Four vitamin K–dependent factors||Thrombin-fibrin clot||Factor Xa–fibrin clot||Factor Xa–fibrin clot|
|Testing||Requires regular blood tests (PT/INR)||None||None||None|
|Diet restrictions||Many diet restrictions||None||None||None|
|DOSE (daily)||Varies according to PT/INR||75–150 mg twice/day||10–15 mg||2.5–5 mg twice/day|
|Elimination half-life||20–60 hr||12–17 hr||5–13 hr||6–12 hr|
|Modification for implant surgery||Not recommended||MD consult; usually discontinuation||MD consult; usually discontinuation||MD consult; usually discontinuation|
Novel Oral Anticoagulant (NOACs).
Because of the disadvantages of Coumadin-based medications, new anticoagulant drugs have recently come to the market without the associated disadvantages of warfarin. The direct thrombin inhibitors have a wide therapeutic index, less complex pharmacodynamics, fewer drug and food interactions, and a very predictable response that makes routine blood testing unnecessary.10 These targeted anticoagulants bind directly to thrombin and block the interaction with its substrates. Unfortunately, there is no reversal agent or antidote for these drugs to counteract the anticoagulant effect at this time, which may lead to serious issues when uncontrolled bleeding occurs (Table 7.2).
Medications That Increase Bleeding7
|Medication||Effect on Bleeding|
|Alcohol||Warfarin enhanced by large amounts of alcohol|
|Analgesics||Bleeding enhanced by aspirin effect on platelets|
|Antibacterials||Warfarin enhanced by cephalosporins, erythromycin and metronidazole. Ampicillin and amoxicillin may increase bleeding|
|Antifungals||Warfarin enhanced by azoles, including miconazole topically|
|Antiinflammatories||Bleeding enhanced by antiplatelet activity of NSAIDs; warfarin may also be enhanced. Corticosteroids may alter warfarin activity|
Antiplatelet medications affect clotting by inhibiting platelet aggregation; however, this occurs by many different mechanisms. Aspirin irreversibly acetylates cyclooxygenase, thus inhibiting the production of thromboxane A2, and clopidogrel (Plavix) selectively inhibits ADP. Thus both have the end result of reducing platelet aggregation. Both of these drugs will affect the platelet function for the life of a platelet, which is 7–10 days. The synthesis of new platelets will overcome the platelet dysfunction, and in 50% to 80% of cases, platelet aggregation returns to normal (Table 7.3).11
Medications That Impair Platelet Function7
|Analgesics and other platelet inhibitors||
Aspirin and other NSAIDs
Ampicillin and derivatives
Benzylpenicillin (penicillin G)
|General anesthetic agents||Halothane|
Diclofenac (Voltaren Cataflam)
Ibuprofen (Motrin, Advil, Nuprin)
Ketoprofen (Orudis, Actron)
Naproxen (Naprosyn, Aleve)
The combination of aspirin and clopidogrel produces additive and possible synergistic effects because the two medications block complementary pathways in the platelet aggregation cascade. Rarely will physicians allow the complete withdrawal of both of these medications as the cardioprotective benefits outweigh the potential for bleeding episodes in at-risk patients with cardiovascular disease.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).
NSAIDs have a reversible effect on platelet aggregation, and platelet function is restored once the drug effects are gone. Minor dental implant surgical procedures can be safely performed without altering the NSAID dose.12
Herbal supplements studies have shown as many as 70% of patients do not reveal they are taking herbal supplements and 40% will take herbal supplements within 2 weeks of surgery.13 Some herbal remedies are fairly safe and have been supported by sound medical research. Thus many PATIENTS believe that, because a medication is termed “natural,” it is safe. However, the majority of supplements have no research on their safety and efficacy action because of product variability and minimal regulation. This has led to many natural plant products on the market that are addictive and highly toxic and can complicate surgical procedures. Some of these supplements may prolong bleeding and impair the coagulation process, which may lead to intraoperative and postoperative bleeding episodes (Table 7.4). Supplements should be withdrawn for a minimum of 2 weeks prior to surgery.
Herbal Supplements That Inhibit Hemostasis7
|Cat’s claw||Uncaria tomentosa|
|Devil’s claw||Harpagophytum procumbens|
|Dong quai||Angelica sinensis|
|Evening primrose||Oenothera biennis|
|Ginkgo biloboa||Ginkgo biloba|
|Grape seed||Vitis vinifera|
|Green tea||Camellia sinensis|
|Horse chestnut||Aesculus hippocastanum|
Systemic Bleeding Disorders
Bleeding disorders may directly or indirectly affect the intrinsic or extrinsic pathways of the hemostasis process. The intrinsic pathway affects the activated partial thromboplastin time (aPTT) via factors VII, IX, XI, XII and the extrinsic pathway involves factor VII, which affects the prothrombin time (PT). Any of these intrinsic or extrinsic factors may affect the common pathway, which alters the formation of the fibrin clot. Usually laboratory tests such as partial thromboplastin time (PTT) and PT will reveal the factor deficiency.
Besides factor disorders, there are also congenital disorders that impact hemostasis. Hemophilia is a bleeding disorder that may be very minor or can be a more severe type leading to significant complications. Hemophilia can be classified into type A (Factor VIII) or type B (Factor IX). von Willebrand disease is an inherited disorder that results from the lack of von Willebrand factor, which is a protein within the blood that assists with blood clotting and carrying clotting factors.11 With any type of systemic bleeding disorder, physician consultation is highly recommended (Box 7.2).
Liver disease (e.g., cirrhosis, acute liver failure) is associated with many significant abnormalities of the coagulation system. The coagulation system and the interrelationship with liver function is very complex. Because most patients exhibiting liver disease have impaired production of coagulation factors and thrombocytopenia, medical consultation before any dental implant procedure is recommended.
Evaluation of the Coagulation Process
There are many tests of the coagulation system that determine the susceptibility of the patient to a bleeding episode during or after dental implant surgery.
Prothrombin Time (PT)
The PT test is performed routinely for many patients prior to surgery or to monitor the effects of the anticoagulant warfarin (Coumadin). Basically, this test of the extrinsic pathway measures the time it takes for the patient’s plasma to form fibrin. Usually, the patient’s warfarin dose will be altered depending on PT times. The prothrombin time reference range will depend on the analytical method used; however, it is usually 12-13 seconds. The results should always be interpreted using the reference range from the laboratory.
International Normalized Ratio (INR)
Because of the poor standardization of the prothrombin time, a wide variation in values obtained by laboratories resulted in inconsistent test values. It has become a standard in most laboratories to perform a correction of the prothrombin time, or to “normalize” the result. This normalized test is called the INR (international normalized ratio), and it is much more accurate in the assessment of a patient’s bleeding time. A normal INR is 1.0 %. However, in anticoagulated patients, the INR will be higher, usually within the therapeutic range of 2.0% to 3.5%. The target anticoagulation level differs for each patient because the anticoagulation will require different therapeutic INR levels. Prolonged INR and PT values are indicative of liver disease, warfarin treatment, or vitamin K deficiency.
Partial Thromboplastin Time (PTT)
The PTT test is usually performed for many patients prior to surgery and to monitor the effect of anticoagulation using heparin. The test measures the intrinsic pathway and factors V, VIII, IX, X, and XI. The formation of the blood clot requires the participation of a series of proteins, and deficiency of any of these will result in abnormal values. The test is expressed in seconds compared to the number of seconds it takes a control normal plasma sample to clot. The most common causes of an abnormal PTT are a hereditary deficiency of Factor XI and von Willebrand disease. Ideally, the PTT value should be approximately 1.5 to 2.5 times the mean normal value.
The bleeding time test is a rather old method of determining platelet function. The Ivy method is the most common technique, which involves a superficial (less than 1 mm deep), small (1 cm long) cut made on the skin of the forearm using a special instrument. The time it takes for the cut to stop bleeding is a test of the function of the platelets. The normal value is usually less than minutes. A prolonged bleeding time is a result of decreased number of thrombocytes or impaired blood vessels.
A platelet count is a test that calculates the number of platelets. Normally, the platelet count should be 100,000–400,000 cells/mm3. Counts less than 100,000 mm3 (thrombocytopenia) can be associated with significant intra- and postoperative bleeding.
The platelet is synthesized by the bone marrow and broken down by the spleen. Abnormalities that would cause a decreased number of platelets are either inherited or acquired, with acquired being rather rare.
Interuption of Anticoagulant Therapy13a
With dental implant patients, interruption of anticoagulation temporarily increases thromboembolic risk. However, continuing the anticoagulation medication may increase the risk of bleeding episodes for the patient (depending on the procedure). The PHYSICIAN should be consulted and perioperative management of anticoagulation should be based on their recommendations. Unfortunately, most anticoagulation interruption approaches are based on expert opinion. Thrombotic and bleeding risks may vary depending on patient and procedure as data from randomized trials are not available to generally guide practices. Most physicians will take the following factors in consideration prior to recommendation:
• Estimate thromboembolic risk. When a higher thromboembolic risk exists, the importance of minimizing the interval without anticoagulation is critical. Most patients being treated for atrial fibrillation, recommendations are based on age and comorbidities. If thromboembolic risk is transiently increased (e.g., recent stroke, recent pulmonary embolism), usually elective surgery is delayed until the risk returns to baseline. The most common issues that increase thromboembolic risk are atrial fibrillation, prosthetic heart valves, and recent venous or arterial thromboembolism (e.g., within the preceding three months).
• Estimate bleeding risk. When the procedure is classified as a higher bleeding risk, there is a greater need for perioperative hemostasis measures and a longer period of anticoagulant interruption. The risk of bleeding is usually determined by the type of surgery and invasiveness of the procedure. Patient comorbidities (e.g., older age, decreased renal function) and current medications that affect hemostasis should also be taken into consideration. Usually with dental implant surgery, bleeding risk is most likely to be classified as “low risk.”
• Determine the timing of anticoagulant interruption. The timing of anticoagulant interruption depends on the specific anticoagulant the patient is receiving. For example, warfarin and aspirin usually requires earlier discontinuation than the shorter-acting direct oral anticoagulants (e.g., dabigatran, rivaroxaban, apixaban, edoxaban).
Techniques to Decrease and Control Bleeding
The need to control gross bleeding is paramount for successful surgery because insidious and continuous loss of blood from arteries, veins, or capillaries can become significant if bleeding is not controlled. Dental implant clinicians have numerous options for maintaining hemostasis, which include mechanical, thermal, pharmacologic, and topical agents.
The most common primary mechanical method to control bleeding is to apply direct pressure or compression on the bleeding site along with repositioning the patient. Secondary mechanical methods include suturing, clamping the blood vessel with hemostats, and ligating the bleeding vessel with suture material.
When significant bleeding occurs, maintaining the patient in a supine position is not recommended because of increased bleeding (head below the heart). Hydrostatic pressure occurs within the vascular system because of the weight of the blood vessels and is dependent on gravity. The pressure is decreased in any vessel above the heart and increased in blood vessels below the heart. Studies have shown that in an upright position, the average pressure at the level of the heart is 100 mm Hg. Vessels in the head and neck averaged 49 mm Hg and 186 mm Hg at the foot level.14 Repositioning the patient to an upright position (head above the heart) will not stop the bleeding; however, it will significantly decrease the hemorrhage (studies have shown a decrease up to 38%) (Fig. 7.4).15
If significant intraoperative bleeding occurs, the ideal treatment should involve immediate application of pressure to the surgical site. Pressure or compression directly on the blood vessel will allow for platelet aggregation and initiation of the coagulation cascade. Pressure may be applied manually or by the patient biting forcefully on a gauze dressing. Pressure should be maintained for at least 3 to 5 minutes to allow the formation of a blood clot. Caution should be exercised to not remove the gauze too early because this may dislodge the clot. Ideally, 3 × 3 or 4 × 4 gauze should be utilized because 2 × 2 gauze may be accidentally aspirated. In primary bleeding, pressure is the simplest and fastest method to control bleeding prior to the use of hemostatic measures.
Suturing plays a significant role not only in obtaining primary closure for ideal healing but also for maintaining hemostasis (direct vs. indirect). Direct placement of a suture (ligation) is used when there is access to a deep bleeding vessel. The suture is placed by entering the tissue at least 4 mm from the bleeding vessel, 3 mm below the vessel, and 4 mm exiting the tissue. This will ligate or occlude the vessel as long as it is placed proximal to the bleeding area. A figure-eight suture technique is ideally utilized (Fig. 7.5A).
Indirect suture placement is utilized to retract the tissue and minimize bleeding via pressure from the accumulated tissue. This is most often used as tie-backs when reflecting an edentulous mandible (cuspid to molar bilaterally). And lastly, good suturing technique is paramount for preventing reactionary bleeding after surgery. Ideally, interrupted or mattress sutures should be placed in conjunction with continuous sutures to maintain closure. A suture material that exhibits high tensile strength is recommended, such as polyglycolic acid (e.g., Vicryl) (Fig. 7.5B–C). The interim prosthesis should be modified to have no direct pressure on the wound site and this may dislodge the sutures.
Clamped Vessel With Hemostat Forceps
When local measures are not successful in controlling bleeding, a hemostat may be utilized to clamp the blood vessel. Usually a curved Kelly hemostat may be used to clamp the vessel to control the bleeding via two mechanisms:
1. Occluding the vessel and damaging the blood vessels wall to stimulate clotting. This clamping pressure should be maintained for approximately 2–3 minutes, which will usually allow for hemostasis. However, this method may be unreliable because the clot may become dislodged and postoperative bleeding may occur after removal of the hemostat.
2. A more successful technique in controlling bleeding is to use fine-pointed hemostats (Kelly hemostats) and ligate the bleeding vessel with suture material. The vessel should be clamped to obtain immediate hemostasis with the tip of the hemostat extending beyond the vessel. A clamped vessel may be ligated with suture material such as an absorbable suture with high tensile strength (e.g., Vicryl). A tie should be placed around the hemostat, extending to the vessel. The hemostats are then removed, and two additional throws are made with the suture. Usually, bleeding from vessels of 2 mm or greater diameter should be ligated. Direct ligation of the bleeding blood vessel is usually the most effective technique in stopping arterial blood flow. However, exposure and identification may sometimes be extremely difficult (Fig. 7.6).
The use of electrosurgery or lasers to reduce bleeding is a common alternative technique to mechanical methods. However, thermal techniques do have drawbacks, such as episodes where bleeding is present in deeper tissue with limited access or from multiple capillaries, in which maintaining hemostasis may be very difficult.
Electrocauterization, developed in the 1930s, has been one of the most common hemostatic techniques because of its low cost, accessibility, ease of use, and effectiveness. Electrocautery is the process of destroying tissue using heat conduction with a probe that is heated by an electric current. Different procedures may be completed with the use of high–radio frequency alternating current for cutting, coagulating, and vaporizing tissues. Electrocautery is most effective on small vessels and may be utilized in two modes: monopolar and bipolar (Fig. 7.7).
Monopolar electrosurgery delivers current using different types of waveforms (i.e., modes). The coagulation mode utilizes an interrupted waveform, which generates heat, thereby coagulating a cell, a phenomenon also termed fulguration. The cutting mode is low energy, which produces a cutting effect to vaporize tissue with minimal hemostasis. The blend mode simultaneously cuts tissue and coagulates bleeding. This technique is often difficult to use in implant surgery because access and a relatively dry field is needed to cauterize the vessel. A dry field is needed for the effective electrical current to pass through the tissues. A high-speed plastic, not metal, suction tip should be used to maintain a dry field.